title: Protective effect of Bajijiasu against β-amyloid-induced neurotoxicity in PC12 cells.
abstract: Beta-amyloid peptide (Aβ), a major protein component of senile plaques associated with Alzheimer's disease (AD), is also directly neurotoxic. Mitigation of Aβ-induced neurotoxicity is thus a possible therapeutic approach to delay or prevent onset and progression of AD. This study evaluated the protective effect of Bajijiasu (β- D-fructofuranosyl (2-2) β- D-fructofuranosyl), a dimeric fructose isolated from the Chinese herb Radix Morinda officinalis, on Aβ-induced neurotoxicity in pheochromocytoma (PC12) cells. Bajijiasu alone had no endogenous neurotoxicity up to 200 μM. Brief pretreatment with 10-40 μM Bajijiasu (2 h) significantly reversed the reduction in cell viability induced by subsequent 24 h exposure to Aβ25-35 (21 μM) as measured by MTT and LDH assays, and reduced Aβ25-35-induced apoptosis as indicated by reduced annexin V-EGFP staining. Bajijiasu also decreased the accumulation of intracellular reactive oxygen species and the lipid peroxidation product malondialdehyde in PC12 cells, upregulated expression of glutathione reductase and superoxide dismutase, prevented depolarization of the mitochondrial membrane potential (Ψm), and blocked Aβ25-35-induced increases in [Ca(2+)] i . Furthermore, Bajijiasu reversed Aβ25-35-induced changes in the expression levels of p21, CDK4, E2F1, Bax, NF-κB p65, and caspase-3. Bajijiasu is neuroprotective against Aβ25-35-induced neurotoxicity in PC12 cells, likely by protecting against oxidative stress and ensuing apoptosis.
authors.affiliation: Southern Institute of Pharmaceutical Research, South China Normal University, Guangzhou, People's Republic of China.
authors.forename: Di-Ling
authors.initials: DL
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Ou
authors.initials: O
authors.lastname: Shuai
authors.forename: He-Ming
authors.initials: HM
authors.lastname: Zhang
authors.forename: Song-Hao
authors.initials: SH
authors.lastname: Liu
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D050687:E2F1 Transcription Factor / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D020836:Protein Structure, Quaternary; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013059:Spectrum Analysis, Raman; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004187:Disaccharides; D004365:Drugs, Chinese Herbal; D050687:E2F1 Transcription Factor; C493755:E2f1 protein, rat; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009498:Neurotoxins; D051028:bcl-2-Associated X Protein; C000588575:fructofuranosyl-(2-2)-fructofuranosyl; D051358:Cyclin-Dependent Kinase 4; D053148:Caspase 3; D002118:Calcium